Neural crest cells undergo an extensive migration during embryonic development. They localize precisely in various embryonic regions, and ultimately differentiate into diverse cell and tissue phenotypes such as pigment cells, sensory and autonomic ganglia, neurosecretory cells, and skeletal and connective tissue of the head and face. The various regions in which crest cells localize exhibit characteristic differences in the kinds and amounts of glycosaminoglycans in the extracellular matrix. We propose to continue our analysis of (1) how cellular interactions, and the associations between cells and the extracellular matrix affect crest cell migration and localization; and (2) how these interactions influence the choice and expression of differentiative pathways by crest cell populations. We will exploit the existance in mice of a number of mutants affecting neural crest development. These result in various alterations of pigment cell distribution, altered distribution of sensory and autonomic neurons, and some cranio-facial lesions. Some of these mutants are recessive embryonic lethals. In addition, we will combine cell culture techniques with various histochemical and biochemical procedures to analyze the role of external macromolecules in regulating the extent of cell association and the consequent expression of crest cell phenotypes.